Title: Psychoactive Drugs
1Psychoactive Drugs
2I. How drugs are handled by the body?
- 1. Absorption into the body.
- 2. Distribution of the drug through the
body, including the fetus, at time drug is taken. -
- 3. Metabolism the detoxification of the
drug by the body (liver). Most drugs are broken
down into metabolites (by-products or waste) that
no longer exert an effect. -
- 4. Elimination of the drug, usually
excreted through urine. -
3Six routes of drug entry into body
- 1. Orally (tablets, capsules, liquid)
- 2. Rectally (suppositories)
- 3. Intravenous (injected in liquid form
through a needle into the skin) - 4. Inhaled through the lungs (as gases,
vapors, or particles) - 5. Through skin (patches on skin)
- 6. Through mucous membranes (snorting or
sniffing under tongue) -
4How drugs act on the system
- The pharmacological, physiological, or behavioral
effects induced by a drug follow their
interaction with receptors. - This is called pharmacodynamics involves the
mechanisms of drug action that occur at the
molecular level.
5Drugs produce effects by
- binding to interacting with specialized
receptors, located on the synapses of neurons.
6What are receptors?
- A receptor is a large molecule on the cells
surface where endogenous compounds
(neurotransmitters) induce their normal effects.
- Usually only 1-2 neurotransmitters is specific
enough to fit or bind to a specific receptor.
7Binding to receptors
- 1. A drug that binds to a receptor normally
occupied by a given transmitter can initiate a
cellular response similar or identical to that
exerted by the transmitter. - The drug mimics the action of the transmitter.
Here, the drug is an agonist for that
transmitter. - 2. A drug that binds to a receptor blocks the
neurotransmitter from stimulating the cell is
called an antagonist.
8II. Dose-Response Relationships
- A dose-response curve may be plotted as
- the dose of a drug given as a function of the
of people who show an effect at a given dosage.
9Drug Effectiveness
- The dose of a drug that produces the desired
effect in 50 of subjects tested is called the
ED50. - The lethal dose for 50 of subjects (animals) is
called the LD50. - The ratio of the LD50 to the ED50 is used as an
index of the relative safety of the drug is
called the therapeutic index
10III. Drugs
- A. ALCOHOL (ethanol)
- Alcohol is found in different concentrations
in liquid - -12 in wine
- -3.5-5 in beer
- -40-50 in liquors
- It is most often expressed as proof which is
twice the percent concentration (i.e., 80 proof
40 ethanol).
11Alcohol absorption
- Alcohol readily diffuses across all biological
membranes is completely absorbed by the entire
GI tract. - Alcohol usually takes 30-90 minutes to reach
peak levels in the blood. - About 20 of a single dose of alcohol is
absorbed directly via the stomach. - The remaining 80 is absorbed rapidly by the
large intestine.
12Alcohol metabolism
- 85 by liver
- 5-by lungs (can be detected by breath)
- 15- broken down by stomach enzymes.
- A full stomach reduces a persons blood alcohol
level, because the enzymes have longer time to
metabolize the alcohol.
13Who has the higher blood alcohol level, men or
women?
- Women!!!
- 1. Women --50 less gastric metabolism of
alcohol, because they have lower levels of
gastric enzymes. - 2. Since men have greater ratio of muscle to fat
than do women, alcohol is more diluted in their
blood (fat has little blood supply in contrast to
muscle). -
14What are the effects of alcohol?
- 1. Physiological effects-
- Slows Respiration (CNS depressant)
- Sedative effects are additive when combined with
other depressants (e.g., barbituates). - Dilates blood vessels in skin (decreases body
temp blushing). - Lowers cholesterol (low doses) by lowering LDL
increasing HDL. - May cause heart damage (high doses-5 drinks per
day). - May cause liver damage (high doses over time)
-
152. Psychological effects
- Behavioral disinhibition (low doses)
- Euphoria (low to moderate doses)
- Violent or irascible mood (moderate to high
doses) - Memory, concentration, insight are impaired
- Reaction time is impaired
- Motor system is impaired (cerebellum)
-
16How does alcohol produce its effects?
- 1. Alcohol is a GABA agonist, it facilitates
expression of GABA (inhibitory transmitter).
Contributes to behavioral disinhibition, motor
slowing. -
- 2. Alcohol inhibits glutamate (excitatory
system). Receptors, which may cause cognitive
effects of alcohol intoxication, such as slurred
speech memory loss. - Alcohol increases levels of dopamine serotonin,
likely providing both euphoric sedative
effects.
17B. MARIJUANA
- Dried crushed leaves flowering tops of the
hemp plant, Cannabis sativa. - Major ingredient-- delta-9-tetrahydrocannabinol
(THC) - Marijuana has 2-5 THC
- May be smoked, chewed, or eaten (in baked goods).
18What are effects of marijuana?
- 1. Physiological effects
- Produces analgesia
- Has antiemetic properties (decreases nausea
vomiting) - Increased HR blood pressure
- Dilated blood vessels in eyes (bloodshot eyes)
- Sedative effects
192. Psychological effects
- Shifts in emotion
- Disrupted attention
- Impaired STM
- Altered sensory perception
- Time distortions (time moves more slowly)
- Motor activity impaired
- Hallucinations (with heavy doses)
- Panic (with heavy doses)
20How does marijuana produce its effects?
- We have cannabis receptors in the brain. These
receptors are found in the - 1. basal ganglia (fine motor system)
- 2. cerebellum
- 3. cortex (especially the frontal lobe)
- 4. hippocampus
- We dont have any cannabis receptors in the
brainstem. THC does not affect basal body
functions.
21Do we have a transmitter substance like THC in
our brains?
- Yes!!! We have anandamide which binds to
cannabinoid receptors produces cannabinoid-like
pharmacological effects.
22C. HALLUCINOGENS
- 1. LSD
- First synthesized in 1938, as a compound of ergot
(a fungus that grows on rye) by Hoffman. - Hoffman accidentally ingested the drug noticed
its unusual effects. - During 1950s, LSD was used as a model for
examining treating psychosis was also used in
therapy.
23LSD administration
- Is taken orally.
- ED50 is 25 micrograms to 300 micrograms.
- Usually is found on sugar cubes, stamps, candy
dots - Is absorbed within 1 hour peaks in 3 hours.
- Duration 6-8 hours.
24What are the effects of LSD?
- 1. Physiological Effects
- Slight increase in body temperature
- pupil dilation
- slightly increased HR blood pressure
- dizziness nausea
252. Psychological Effects
- 1. Altered perception, thinking, emotion,
arousal - 2. time distortions (slowed)
- 3. Intense visual auditory hallucinations
(trasers) - 4. Cross-sensing (hearing colors seeing
sounds) - 5. emotions shift rapidly (happiness to pit
of despair) - 6. tension anxiety make lead to panic
- 7. psychotic experience
26How does LSD produce its effects?
- LSD exerts its effects by interacting with
serotonin receptors (5-HT receptors). - Most researchers argue its a serotonin agonist.
272. MESCALINE
- Comes from the crown or button of the peyote
cactus. - The crown is dried into a hard brown disk that
softens when ingested. - Is absorbed in 1-2 hours.
- Effects occur between 3.5 4 hours after
ingestion. Vivid hallucinations most salient. - --trip is long (10 hours)
- Right frontal activity seems to be high in people
on mescaline. Agonistic for norepinephine
serotonin.
283. PSILOCYBIN
- Found in mushrooms (genera Psilocybe).
- Mushrooms are eaten raw.
- mushrooms grow through out world, including
northwestern US. - It peaks in about 2 hours, effects
- last 6-10 hours.
29How does it produce its effects?
- It appears to exert its effects as a serotonin
agonist that stimulates 5-HT receptors especially
in the frontal areas.
304. MYRISTIN ELEMICIN
- Are agents found in nutmeg mace, two common
household spices. - ED50--1-2 teaspoonsusually brewed in tea
- Within 2-5 hours, you get symptoms similar to LSD
(euphoria, visual hallucinations, psychosis,
etc.) - However, most people experience vomiting, nausea,
tremors prior to the trip making it a one
time event for many.
31D. STIMULANTS
- In general these drugs
- increase behavioral activity
- elevate mood
- increase alertness
- allay sleep
- increase brains metabolic neuronal activity.
321. COCAINE
- Comes from the coca plant (Erythroxylon coca)
found in South America. - The active alkaloid in E. coca was isolated in
1855, purified in 1860, named cocaine. - In late 1800s, cocaine was used as an anesthetic
(spinal, local), was added to medicines
Coca-Cola. - It was banned from use in medicines beverages
in 1914 in the Harrison Narcotic Act. -
33COCAINE (history)
- By 1930s, amphetamines replaced the popularity of
cocaine. - 1960s- cocaine makes a comeback when amphetamines
become pricey. - 70s-80s cocaine becomes chic with jetset.
- cheap crack cocaine becomes hit in poor
areas. -
34Forms of cocaine
- Cocaine can be snorted, smoked, taken orally, or
injected intravenously. - Powdered cocaine (cocaine hydrochloride) 25 mg
per line. - Crack cocaine- (250 mg-1 gm) per smoke.
35Physical Effects
- Vasoconstrictor
- Increases norepinephrine dopamine
- Tachycardia
- Stroke, seizure, heart attack
- Increased blood pressure
- Local anesthetic
36Psychological Effects
- Euphoria
- Elevated mood
- Agitation
- Flight-of-ideas
- Grandiose thoughts
37How does it produce its effects?
- Cocaine blocks reuptake of dopamine,
norepinephrine, serotonin, thereby increasing
them in the CNS. - Increasing dopamine levels in dopaminergic reward
system results in euphoric/addictive effects of
drug.
382. AMPHETAMINES- Effects
- Vasoconstriction
- Hypertension
- Tachycardia
- Increased motor activity
- Loss of appetite
- Restlessness/tremors
- hallucinations (amphetamine psychosis)
- Paranoid delusions
39Amphetamines-today
- 1. Therapeutic use in the treatment of
narcolepsy ADHD. - 2. To treat compulsive misuse of methamphetamine
(amphetamine derivative).
40How do amphetamines cause their effects?
- They cause release of norepinephrine dopamine
from presynaptic storage sites in nerve
terminals. - Peripheral NS activity --increased norepinephrine
41ICE- form of methamphetamine
- Was originally used to treat ADHD, not mostly a
an illegal street drug. - Street names of drug Speed, crystal, crank, go,
ICE. - Methamphetamine--orally, by IV injection,
snorted. The base form (ICE) can be smoked. - ICE-methamphetamine, crack-cocaine. Its the
free-base, smokable form of the parent compound.
42NONAMPHETAMINE BEHAVIORAL STIMULANTS
- Does not have the same nucleus structure of
amphetamines, but shares same action of
increasing SNS activation. - One of the most common of these is
- Methylphenidate (Ritalin)
43Methylphenidate (Ritalin)
- Has a short half life (2-4 hours).
- Concerta--A new sustained-release formulation of
methylphenidate--taken in the early AM, it is
good through the day. - Is much more expensive than regular Ritalin.
44How does Ritalin exert its effects?
- Thought to increase norepinephrine dopamine, by
blocking reuptake in the presynaptic neuron.
Also stimulates the release dopamine. - Once thought to exert its behavioral effects
(calming) via increased dopamine, it is now
thought that effects may be result of increased
serotonin activity (or balance of both).
453. CAFFEINE
- The most common psychoactive drug in world.
- Consumed -80 of adult population.
- 1 cup of coffee---50-150 mg of caffeine.
- Caffeine content of chocolate--25 milligrams per
ounce. - Average intake 3-5 cups of coffee every day.
46Absorption
- Significant blood levels of caffeine are reached
in 30 to 45 min with complete absorption in 90
min. - Peaks in about 2 hrs decreases thereafter.
- The half-life is about 3.5 to 5 hours in most
adults.
47Effects
-
- tachycardia
- Increased Blood pressure
- Vasoconstriction
- Diurectic
- Increased mental activity alertness
- Increased wakefulness
- Agitation
- Tremors
- Anxiety
- Insomnia
48 - HOW DOES CAFFEINE EXERT ITS EFFECTS?
- Caffeine exerts its effects by blocking adenosine
receptors. - Adenosine is a neuromodulator that influences the
release of several neurotransmitters in the CNS. - It appears to exert sedative, depressant,
anticonsulsant actions. Thus, blocking adenosine
causes anxiogenic effects.
49E. OPIATES
- A group of addictive sedatives that in
- moderate doses relieve pain induce sleep.
- The original principle opiate was opium, which is
extracted from poppy seeds of the poppy plant
(papaver somniferum). - The psychoactive ingredient in opium is morphine,
named for Morpheusthe Greek God of dreams. - Two drugs are found in the exudate of the poppy
morphine codeine.
50OPIATES-History
- Opium--has been used for thousands of years to
produce euphoria, analgesia, sleep, relief from
diarrhea cough. - Ancient Greece Rome-- through the 16th-
17th-centuries, opiums medicinal recreational
uses were well established. - A mixture of opium and alcohol, called laudanum,
was used to treat practically every disease known
during the 1800s.
51OPIATES-History
- During the civil war, opium addiction was a
widespread problem. - By 1914, the Harrison Narcotic Act was passed and
the use of most opioid products was controlled.
52Opiates vs. Opioids
- Opiate-- is a drug that is extracted from the
exudates of the poppy. - E.g., morphine and codeine.
- An opioid is any exogenous drug (natural or
synthetic) that binds to an opiate receptor
produces agonist or morphine-like effects. - E.g., heroin
53Endorpins (morphine-within)
- Endorphins --any endogenous substance (naturally
occurring in the body) that exhibits
pharmacological properties of morphine. - We have 3 families of endorphinsenkephalins,
dynorphins, beta-endorphins.
54MORPHINE
- Is still the most potent pain reliever available
(no other drug has its clinical effectiveness). - Is administered orally, rectally, or by
injection. Absorption is slow only 20 of the
drug reaches the CNS. - Is broken down by liver produces metabolites
(morphine t-glucoronide) that are 10 to 20-fold
more potent that morphine itself. These continue
exerting analgesic effects. - Morphines half-life 3 to 5 hours.
55MORPHINE-DRUG TESTING
- For 2 to 4 days following opiate use, urine
screening tests can be used to detect codeine
morphine as well as their metabolites. - Heroin use can be tested for indirectly. Heroin
is metabolized to morphine also often contains
acetylcodeine (metabolized form of codeine). - Although the tests cannot accurately determine
which drug (heroin, codeine, morphine) was
present.
56WHAT ARE EFFECTS OF MORPHINE?
- Analgesia
- Relaxation
- Euphoria
- Sedation
- Sense of transquility
- Reduced anxiety
- Respiratory depression
- Cough suppression
57HOW DOES MORPHINE EXERT ITS EFFECTS?
- Morphine, like other opiates opioids, exert its
effects by stimulating opiate receptors widely
distributed through the CNS (brain, brain stem,
spinal cord).
58 CODEINE
- Is usually combined with aspirin or acetaminophen
for the relief of mild to moderate pain. - Half-life--3 to 4 hours.
- Codeine is metabolized by hepatic cytochrome
CYP2D6 enzymes to morphine, many of its effects
may be the result of morphine actions. - Using serotonin-specific antidepressants can
block the pain relief of codeine, because they
block the conversion of codeine to morphine.
59HEROIN (diacetylmorphine)
- Is produced by a slight modification of the
chemical structure of morphine. - It cross the blood-brain barrier very rapidly,
leading to an intense rush when it is either
smoked or injected intravenously. - It is metabolized to monoacetylmorphine
morphine. - Clinical use of heroin is legal in Great Britain
Canada.
60F. ANTIDEPRESSANTS
- A broad class of drugs used to treat depression.
- What is depression???
- A state of great sadness characterized by
feelings of despair, worthlessness, hopelessness,
withdrawal from other. - Its the common cold of psychopathologyweve
all had symptoms at some point.
61Major depression DSM diagnosis made if
- Person has 5 of the following symptoms (next
slide) for at least 2 weeks. - Depressed mood or loss of interest pleasure in
enjoyable activities (anhedonia) must be included
in symptoms.
62Symptoms of major depression
- 1. Depressed mood.
- 2. Loss of interest and pleasure.
- 3. Significant weight loss or weight gain.
- 4. Difficulty in sleeping-Insomnia or
- hypersomnia.
- 5. Shift in activity level, psychomotor
retardation, or agitated. - 6. Fatigue or loss of energy.
- 7. Negative self-concept.
- 8. Difficulty concentrating.
- 9. Recurrent thoughts of death or suicide.
631. Tricyclics
- E.g., imipramine (Tofranil) and amitriptyline
(Elavil). - These prevent reuptake of both norepinephrine
serotonin by the presynaptic neuron. - 2. Monoamine oxidase (MAO) inhibitors -
tranylcypromine (Parnate) - Keeps enzyme monoamine oxidase from
deactivating neurotransmitters, thereby
increasing the levels of both serotonin and
norepinephrine.
643. Selective serotonin reuptake inhibitors
(SSRIs) fluoxetine (Prozac) sertraline
(Zoloft).
- Selectively blocks reuptake of serotonin.
- Efficacy of all three classes of drugs about the
same (50-70 effective). - Side effects fewer in SSRIs. Tricyclics can be
dangerous.